(S)-2-哌嗪甲醇

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of compound 1B (207 mg, 1.78 mmol) in CH3CN/DMA/H2O (1 mL, 0.3 mL, 0.7 mL) cooled to 0° C. was added dropwise CBZ-OSu (444 mg, 1.78 mmol) in DMA (0.5 mL). The reaction was stirred for 15 min at 0° C. then slowly warmed to RT. To the reaction was added H2O (30 mL) and sat'd NaHCO3 (5 mL), and then the product was extracted three times with EtOAc (20 mL). The combined EtOAc layers were washed twice with brine, dried over MgSO4 then concentrated in vacuo to give crude (S)-benzyl 3-(hydroxymethyl)piperazine-1-carboxylate (256 mg). HPLC RT: 1.082 min (4 min Chromolith column TFA). (M+H)+:251. then slowly warmed to RT the product was extracted three times with EtOAc (20 mL) The combined EtOAc layers were washed twice with brine dried over MgSO4 then concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (S)-2-piperazinemethanol (1.25 g) in a mixture of water (12 ml) and triethylamine (3.2 ml) at ambient temperature was treated with a solution of acetic anhydride (1.25 ml; 1.32 mmol) in water (25 ml). The mixture was stirred at ambient temperature for 1 h, and anhydrous sodium carbonate (2 g) was added. The solvent was removed in vacuo. The residue was purified by flash column chromatography using dichloromethane:methanol:ammonia, 75:10:2 as eluant to give the title compound as a pale yellow oil (0.6 g). The solvent was removed in vacuo The residue was purified by flash column chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of the product of stage (ii) (0.080 g) in dry acetonitrile (10 ml) was treated with a solution of methyl chloroformate (71 mg; 0.75 mmol) in dry acetonitrile (3 ml) over a 5 min period. The mixture was stirred at ambient temperature for 30 min and aqueous sodium carbonate solution (1 ml) was added. The solvent was removed in vacuo and the aqueous residue was extracted with dichloromethane (3×25 ml) and chloroform (3×25 ml). The extract was washed with aqueous sodium carbonate solution (5 ml: 1M), and the combined extracts were dried and evaporated in vacuo to give the title compound as an oil (0.1 g). The solvent was removed in vacuo the aqueous residue was extracted with dichloromethane (3×25 ml) and chloroform (3×25 ml) The extract was washed with aqueous sodium carbonate solution (5 ml: 1M) the combined extracts were dried evaporated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of compound 1B (207 mg, 1.78 mmol) in CH3CN/DMA/H2O (1 mL, 0.3 mL, 0.7 mL) cooled to 0° C. was added dropwise CBZ-OSu (444 mg, 1.78 mmol) in DMA (0.5 mL). The reaction was stirred for 15 min at 0° C. then slowly warmed to RT. To the reaction was added H2O (30 mL) and sat'd NaHCO3 (5 mL), and then the product was extracted three times with EtOAc (20 mL). The combined EtOAc layers were washed twice with brine, dried over MgSO4 then concentrated in vacuo to give crude (S)-benzyl 3-(hydroxymethyl)piperazine-1-carboxylate (256 mg). HPLC RT: 1.082 min (4 min Chromolith column TFA). (M+H)+:251. then slowly warmed to RT the product was extracted three times with EtOAc (20 mL) The combined EtOAc layers were washed twice with brine dried over MgSO4 then concentrated in vacuo